Einfluss von Androgenen und Salzhaushalt auf die renale Mineralokortikoid- und Glukokortikoidrezeptor-Expression von orchiektomierten Wistar-Ratten

Einführung: Der Zusammenhang zwischen Salzlast, Niere und arterieller Hypertonie ist gut definiert. Neuere Erkenntnisse deuten auf eine entscheidende Interaktion des mineralokortikoiden und glukokortikoiden Systems in der Blutdruckregulation hin. Darüber hinaus weisen Geschlechterunterschiede im Blutdruck auf eine modulierende Rolle von Androgenen hin. Wenig ist jedoch über die Wechselwirkung zwischen Androgenen und dem Mineralokortikoidsystem bekannt. Die vorliegende Arbeit untersuchte die Wirkung der Androgensubstitution und des unterschiedlichen Salzstatus auf die renale Expression des Mineralokortikoid- (MR) - und Glukokortikoidrezeptors (GR). Methoden: Männliche Wistar-Ratten im Alter von 8-10 Wochen wurden orchiektomiert und erhielten eine Niedrigsalz- (< 0,03 % NaCl, Leitungswasser) oder Hochsalz-Diät (4 % NaCl, 0,09 % NaCl Trinkwasser) für 5 Wochen. Zusätzlich wurden sie entweder mit Placebo, Testosteronpropionat (Testo: 1 mg/ Tier) oder 5α-Dihydrotestosteron (DHT: 1 mg/ Tier) als tägliche subkutane Injektion für 16 Tage behandelt (jede Gruppe n = 6). Außerdem wurde den Tieren der Androgenrezeptor (AR)-Antagonist Flutamid, der MR-Antagonist Spironolacton bzw. Placebo appliziert. Anschließend wurde der Blutdruck in vivo und Hormonwerte bei Dekapitation bestimmt. Im Fokus wurde die renale mRNA- und Proteinexpression von MR und GR nach Organentnahme untersucht. Ergebnisse: Die Natriumbelastung führte zur Verminderung der MR mRNA als auch Protein-Expression bei den natriumreich ernährten Kontrolltieren. Dieser Effekt konnte durch Spironolacton aufgehoben werden. DHT rief eine Steigerung der MR mRNA Expression hervor, auch bei Tieren, bei denen der AR blockiert war. Interessanterweise führte die AR-Blockade durch Flutamid zu einer signifikanten Hochregulierung der MR mRNA bei Ratten mit einer Hochsalzdiät. Bei den salzarm ernährten Ratten hingegen konnte unabhängig von der Androgenbehandlung die Verminderung der MR mRNA Expression durch Flutamid beobachtet werden. In ähnlicher Weise wurde die GR mRNA Expression bei Ratten bei einer Hochsalzdiät unterdrückt. Dieser Effekt wurde durch Spironolacton aufgehoben. Die GR mRNA Expression wurde durch DHT unabhängig vom Salzstatus hochreguliert. Nach AR-Blockade war dieser Effekt weniger ausgeprägt. Flutamid führte zu einer Hochregulierung von GR mRNA bei den natriumreich ernährten Ratten, während in den natriumarm ernährten Ratten eine Herunterregulation von GR mRNA unabhängig von der Androgenbehandlung beobachtet werden konnte. Schlussfolgerung: Androgene erhöhen die renale MR und GR mRNA Expression in gleicher Weise. Außerdem reguliert Flutamid sowohl die renale MR als auch die GR mRNA Expression in Abhängigkeit vom Salzstatus der Diät, aber unabhängig von der Androgenbehandlung. Diese Daten bestätigen eine Wechselwirkung von Androgenen mit dem renalen Mineralokortikoidsystem und eine mögliche AR-unabhängige Wirkung von Flutamid auf die Blutdruckregulation. Der GR ist bei der Aufrechterhaltung der Natrium- und Wasser-Homöostase bereits unter physiologischen Bedingungen beteiligt.Introduction: An essential link between salt loading, renal function and arterial hypertension is well defined. Furthermore, sex differences in blood pressure point to a modulating role of androgens. New insights suggest crucial interdependent actions of the mineralocorticoid and glucocorticoid system in blood pressure regulation. But little is known about the interaction between androgens and the mineralocorticoid system. This study examined the effect of androgen treatment and different salt status on renal mineralocorticoid (MR) and glucocorticoid receptor (GR) expression. Methods: Male Wistar rats aged 8-10 weeks were orchiectomized and put on a lowsalt (chow < 0.03 % NaCl, tap water) or high-salt diet (chow 4 % NaCl, water 0.09 % NaCl) for 5 weeks. They were treated with either placebo, testosterone propionate (Testo: 1 mg/ animal) or 5α-dihydrotestosterone (DHT: 1 mg/ animal) as a daily subcutaneous injection for 16 days (each group n = 6). In addition, the animals received the androgen receptor (AR) antagonist flutamide, the MR antagonist spironolactone or placebo, respectively. In vivo measurements were made for blood pressure and hormone levels measured after decapitation. Renal mRNA and protein expression of MR and GR were assessed after animal sacrifice. Results: Sodium loading led to a downregulation of MR mRNA in control animals. This effect was abolished by spironolactone. DHT caused an upregulation of MR mRNA, but also in animals where AR was blocked. Interestingly, AR blockade by flutamide led to a significant upregulation of MR mRNA in rats on a high-salt diet, whereas downregulation of MR mRNA by flutamide independent of androgen treatment could be seen in salt-restricted rats. Similarly, GR mRNA expression was suppressed in rats on a high-salt diet. This effect was abolished by spironolactone. GR mRNA expression was upregulated by DHT independent of the salt status. After AR blockade this effect was less pronounced. Flutamide itself led to an upregulation of GR mRNA in rats on a high-salt diet, whereas a downregulation of GR mRNA was seen in salt-restricted rats independent of androgen treatment. Conclusions: Androgens increase renal MR and GR mRNA expression equally. Furthermore, flutamide regulates both renal MR and GR mRNA expression depending on the salt status of the diet in orchiectomized rats, but irrespective of androgen treatment. These data reflect a crosstalk of androgens with the renal mineralocorticoid system and a possible AR-independent effect of flutamide on blood pressure regulation. GR contributes to maintenance of sodium and water homeostasis physiologically

Effect of risk factors on the outcomes of COVID-19-infected intensive care patients: a single-center retrospective study

Background: To date, little attention has been paid to the impact of risk factors on the outcome of patients with coronavirus disease 2019 (COVID-19) hospitalized in the intensive care unit (ICU). This study was performed to examine the effects of risk factors on death among COVID-19 patients hospitalized in the ICU.&nbsp; Methods: From April 2020 to November 2020, data on 141 COVID-19-infected intensive care patients at 7 Air Force Hospital, Kanpur, were retrospectively retrieved. All analyses were performed using SPSS statistical software (SPSS Inc., Chicago, IL, USA, 15.0). Bivariate and multivariate logistic regression analysis was done to identify independent risk factors. A p-value &lt;0.05 was considered statistically significant. Results: Most of study population were males (69.5%) with mean age of 59.8 ± 17.5 years. Out of 141 patients, 60 (42.6%) patients had comorbidities and 81 (57.4%) patients had no comorbidities. ICU death rates were 46.1%. Bivariate logistic regression analysis revealed that male sex (OR:0.45;95%CI:0.21-0.94), diabetes mellitus (OR:2.96; 95%CI:1.16-7.54), coronary artery disease (OR:2.48;95%CI:0.83-7.37), chronic kidney disease (OR:0.13,95% CI:0.02-1.12), patients with one (OR:1.25,95%CI:0.54-2.86) or more than two comorbidities (OR:1.95,95%CI:0.81-4.70), and who required high flow oxygen therapy (OR:13.30,95%CI:5.81-30.43), non-invasive (OR: 0.10,95% CI:0.02-0.45) and invasive ventilators (OR:0.04,95%CI:0.02-0.09) all were associated with higher ICU death rates. Multivariable logistic regression found following independent risk factors for death: patients with one comorbidity (OR:0.10;95%CI:0.02-0.66), non-invasive ventilator (OR:0.005;95%CI:0.000-0.091), and invasive ventilator (OR:0.003;95%CI:0.000-0.032). Conclusion: Identification of risk factors is of utmost importance to reduce death in COVID-19 infected intensive care patients

Upping the game of taxi driving in the age of Uber

National Research Foundation (NRF) Singapore under its Corp Lab @ University scheme; Fujitsu Limite

Stability Study of Molecularly Doped Semiconducting Polymers

Molecular doping of semiconducting polymers has emerged as a prominent research topic in the field of organic electronics, with new dopant molecules introduced regularly. FeCl3 has gained attention as a p-type dopant due to its low cost, availability, ability to dope high ionization energy copolymers, and its use as a dopant that can be used with anion exchange. Here, we use a combination of UV-vis-NIR spectroscopy, four-probe sheet resistance measurements, and X-ray absorption near-edge structure (XANES) spectroscopy to perform lifetime measurements to assess the stability of the doped polymers over time, which is crucial for evaluating the long-term performance and reliability of the doped films. We used gas chromatography-mass spectrometry (GCMS) to prove that FeCl3 can cause radical side reactions that damage the conjugated polymer backbone, leading to the degradation of the electronic properties. The rate of this degradation is orders of magnitude higher when the film is exposed to air. Anion exchange doping can reduce the [FeCl4]− concentration, but does not necessarily improve the doping lifetime because anion exchange electrolytes can serve as coreactants for the degradation reaction. By comparison, doping with (2,3,5,6-tetrafluoro-2,5-cyclohexadiene-1,4-diylidene)dimalononitrile (F4TCNQ) as the reactive dopant results in lower initial conductivity, but the lifetime of the doped polymer is almost tripled as compared to that of FeCl3 doped polymer films. These findings highlight that the use of FeCl3 as a molecular dopant requires a cost-benefit analysis between higher initial doping levels and lower film stability

Stability Study of Molecularly Doped Semiconducting Polymers

Molecular doping of semiconducting polymers has emerged as a prominent research topic in the field of organic electronics, with new dopant molecules introduced regularly. FeCl3 has gained attention as a p-type dopant due to its low cost, availability, ability to dope high ionization energy copolymers, and its use as a dopant that can be used with anion exchange. Here, we use a combination of UV–vis–NIR spectroscopy, four-probe sheet resistance measurements, and X-ray absorption near-edge structure (XANES) spectroscopy to perform lifetime measurements to assess the stability of the doped polymers over time, which is crucial for evaluating the long-term performance and reliability of the doped films. We used gas chromatography–mass spectrometry (GCMS) to prove that FeCl3 can cause radical side reactions that damage the conjugated polymer backbone, leading to the degradation of the electronic properties. The rate of this degradation is orders of magnitude higher when the film is exposed to air. Anion exchange doping can reduce the [FeCl4]− concentration, but does not necessarily improve the doping lifetime because anion exchange electrolytes can serve as coreactants for the degradation reaction. By comparison, doping with (2,3,5,6-tetrafluoro-2,5-cyclohexadiene-1,4-diylidene)­dimalononitrile (F4TCNQ) as the reactive dopant results in lower initial conductivity, but the lifetime of the doped polymer is almost tripled as compared to that of FeCl3 doped polymer films. These findings highlight that the use of FeCl3 as a molecular dopant requires a cost-benefit analysis between higher initial doping levels and lower film stability